Dual GIP–GLP1-Receptor Agonists In The Treatment Of Type 2 Diabetes: A Short Review On Emerging Data And Therapeutic Potential

Marie Bastin, Fabrizio Andreelli Diabetology-Metabolism Department, Sorbonne Université, ICAN, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, F-75013, FranceCorrespondence: Fabrizio AndreelliDiabetology-Metabolism Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l’Hôpital, Paris cedex 13, 75951, FranceEmail fabrizio.andreelli@aphp.frAbstract: The need for efficient and safe therapy to improve such metabolic diseases as obesity and type 2 diabetes mellitus is currently unmet. The development of dual GIPR–GLP1R coagonists that bind to either one or the other receptor (sequence-mixed dual agonists) has emerged as an innovative therapeutic strategy for obesity and type 2 diabetes. Combined activation of both receptors may act synergistically providing additive effects on glucose and body weight in comparison of GLP1 analogues alone. Preclinical studies have confirmed that GIPR–GLP1R coagonists improve several hallmarks of metabolic syndrome, such as obesity, hyperglycemia, and dyslipidemia. These metabolic benefits have been translated from mice to nonhuman primates and humans. Recent clinical trials have shown that coagonists induce significant benefits on body weight, fasting, and postprandial glucose levels, insulin sensitivity, and total cholesterol. Combined GIP- and GLP1R activators have the potential to become a treatment option for patients with type 2 diabetes.Keywords: incretins, type 2 diabetes, coagonists, GLP1, GIP, body weight